Magnetic markers for surgical guidance

ABSTRACT

An implantable magnetic marker comprising at least one piece of a large Barkhausen jump material (LBJ) containing at least one loop. The coiled marker is deployed to mark a tissue site in the body for subsequent surgery, and a magnetic detection system with a handheld probe excites the marker above or below the switching field required for bistable switching of the marker causing a harmonic response to be generated in a bistable or sub-bistable mode that allows the marker to be detected and localised.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation application of U.S. patentapplication Ser. No. 16/981,860 filed on Sep. 17, 2020, which is thenational phase under 35 U.S.C. § 371 of International Application No.PCT/IB2019/052170 filed on Mar. 18, 2019, which claims priority to andthe benefit of United Kingdom Patent Application No. 1804683.9 filed onMar. 23, 2018, the entire disclosures of each of which are incorporatedby reference herein.

FIELD OF THE INVENTION

This invention relates in general to the field of surgical guidance,more specifically to magnetic markers that aid in locating a lesion forsurgical excision and to systems and methods for detecting such markers.

BACKGROUND OF THE INVENTION

Markers are used to guide surgeons to a region of interest during asurgical procedure, where the site of interest is not physically visibleor palpable, for example a small tumour that needs to be excised.Ideally, such a marker will be deployable through a narrow gauge needlee.g. 18 g to 14 g in order to reduce trauma to the patient. Typically,such markers are less than 10 mm in length so as to be unobtrusive andto minimise trauma. The marker may be placed during a biopsy or othersurgical procedure at a site of interest in the body, for example acancer lesion. The marker is placed under imaging guidance such asultrasound or X-ray/mammography. During subsequent surgery, the markeris detected and localised using a handheld probe which provides audible,visual or other feedback to the surgeon to guide the surgery. Typicallythe marker is excised along with the surrounding tissue.

One such approach is to use a marker containing a radioisotope such asIodine 90 which can be detected using a handheld gamma detection probe.However, use of radioactive materials is closely regulated, making itchallenging to set up a radioactive seed programme in all but thelargest academic hospital centres.

US 2017/252124 (Cianna Medical) discloses a localization system whichuses a combination of radio frequency (RF) and infra red (IR) radiationto detect a marker in the form of an implantable radar antenna. However,this system is limited by the low tissue penetration depth of IRradiation, the need for intimate tissue contact for good IR propagation,and the lack of robustness often associated with an implantable devicecontaining antennae and electronic circuits.

US 2015/264891 (Health Beacons) discloses a further system based onradio frequency identification (RFID) tags that have been used asidentity markers for pets and livestock. The drawback with this approachis that the small RFID tag constitutes a dipole antenna which has‘deadspots’ when approached perpendicular to the dipole axis. This couldcause confusion for surgeons using the system to localize a lesion.Miniaturizing the RFID tag sufficiently for convenient clinicalimplantation is also challenging.

A further approach is discussed in the Applicant's earlier publishedpatent applications (for example, WO 2011/067576, WO 2014/032235 and WO2014/140567) and uses magnetic fields and a magnetic marker with highmagnetic susceptibility. A handheld probe generates an alternating fieldwhich excites a magnetically responsive marker, and detects theresponding magnetic field. This approach is effective for deeper sensingand avoids the drawbacks of RF approaches. However, these systems willdetect any magnetically responsive material in the vicinity of theprobe, such as a ferromagnetic surgical tool or other metallic implanteddevice. This means that for effective operation they need to be usedwith non-ferromagnetic surgical instruments and away from other metallicimplantables. Additionally, such a probe may respond to iron oxidenanoparticle suspensions used for sentinel node detection in breastcancer.

It has therefore proved problematic to provide a marker and detectionsystem that possesses all the properties required for localisinglesions, namely: a marker of a small size (<10 mm long); ability todeliver the marker through a small needle (eg. 16 g-18 g); ability todetect the marker using a handheld probe; and robust for implantationand surgical removal, together with a detection system that is able todistinguish the lesion marker from other magnetically responsivematerials.

Sulla (Utilizing Magnetic Microwires For Sensing In BiologicalApplications, Jnl. of Elec. Eng., VOL 66. NO 7/s, 2015, 161-163)describes the use of glass coated amorphous microwires exhibiting largeBarkhausen jump behaviour for medical applications, in particular as animplant that can be detected magnetically by applying an external fieldusing the bistable behaviour of the microwire. In this respect, ‘LargeBarkhausen Jump’ (LBJ) materials, undergo a rapid reversal of theirmagnetic polarization when excited by an external magnetic field whosefield strength opposing the instantaneous magnetic polarization of thewire exceeds a predetermined threshold value. Thus, the materialexhibits bistable behaviour, reversing between two magnetic polarisationstates. Each reversal of magnetisation generates a magnetic pulse withharmonic components. The profile and number of harmonics is measured(out to many tens of harmonics) to identify the marker from othermaterials. Sulla concludes that a piece of wire 40 mm in length isrequired for functional sensing, but a marker of this length would beunsuitable for lesion localisation as many lesions are only a fewmillimetres in size.

These conditions suggest that this large Barkhausen jump behaviourdescribed in the prior art is unsuitable for use as a lesionlocalisation marker for the following reasons:

-   -   The critical length required for the large Barkhausen jump of        most such materials is greater than 5-10 mm making them too        large for conveniently marking small lesions which may be only a        few millimetres in size.    -   The switching field must be above a threshold H_(sw) in order to        drive the bistable behaviour, requiring large area excitation        and large diameter sensing coils in the tens of centimetre range        that generate large magnetic fields enabling the presence of a        small wire to be detected from a useful range. However, for        surgical guidance, a much more precise localisation of the        marker is needed via a handheld or robotically guided detection        probe. This limits the size of the detection coils to typically        less than 20 mm diameter and thus limits the distance at which a        marker can be detected. If the drive field is also generated in        the probe, the detection ability decreases per the fourth or        sixth order with distance from the probe. Thus while U.S. Pat.        No. 4,660,025 discloses EAS markers excitable with switching        fields of 0.6-4.5 Oe (0.06-0.45 mT), and U.S. Pat. No. 6,230,038        with a switching field of at least 1 Oe, the fields that can be        generated at around 40 mm from a handheld probe are in the        region of 0.5×10-3-0.05 Oe (0.05-5 μT) when current, voltage,        power and temperature range limitations are taken into account        i.e. one to two orders of magnitude lower.    -   For some LBJ materials, the field at which the LBJ response is        initiated increases with frequency, meaning that the wires        become harder to excite at higher frequencies. For this reason,        the prior art specifies frequencies below 3 kHz and preferably        well below 1 kHz. This is undesirable for surgical guidance        where in order to maximise signal to noise ratio from the very        small fields being detected, it is desirable to average the        signal over a number of cycles. Higher frequencies allow more        averaging without the feedback response to the user appearing to        have a lag or delay.

A further drawback of this type of system is the large anisotropy of theresponse from the marker wires, meaning that the response in the axialdirection is much greater than the response in the transverse direction.In the EAS application, this does not present a problem because thesystem only needs to sense the presence of the marker, not its distancefrom the detector, and so large coils and high field strengths enablesatisfactory EAS detection. However, in surgical guidance with ahandheld probe, a response that varies depending on the direction ofapproach will be confusing to the user because the marker will appear tobe a varying distance from the probe depending on the orientation ofapproach.

The Applicant's co-pending Application No GB1801224.5, the contents ofwhich are incorporated herein by reference, describes an implantablemagnetic marker comprising at least one piece of magnetic material thatexhibits a large Barkhausen jump (LBJ) in its magnetisation curve, butwhere the marker is excited below the switching field required toinitiate bistable switching behaviour of the LBJ material of the marker.The marker may also be below the critical length required to initiatebistable switching behaviour of the LBJ material. The concepts of‘critical length’ and ‘switching field’ for LBJ wires are known from forexample Vazquez (A soft magnetic wire for sensor applications, J. Phys.D: Appl. Phys. 29 (1996) 939-949). The marker in GB1801224.5 GB utilisesa newly recognised “sub-bistable” mode of excitation for its LBJmaterial that causes a measurable harmonic response to be sensed evenwhen the excitation field is below that of the ‘switching field’,traditionally considered necessary to initiate the classic bistableswitching behaviour and a harmonic response.

Markers in the art all use straight pieces of LBJ wire. This is becausethe classic switching behaviour occurs through a cascade or dominoeffect in which the magnetic domains in the LBJ wires all flip at onetime, and thus alignment of all the domains with the driving magneticfield is key. Domains not substantially aligned with the field will notflip or switch, meaning that the bistable behaviour of the magneticresponse in which all the domains undergo a rapid reversal ofmagnetisation could not be realised thus resulting in the use ofstraight wires for detection. The use of any other configuration wouldbe counter-intuitive based on the prior art literature.

However, when a straight piece of LBJ wire is excited, the magneticresponse it gives is directional, that is there is a greater responsealong the axis of the wire and a much lower response in a directionperpendicular to the wire. For this reason, the inventors in co-pendingPatent Application No. GB1801224.5, which uses their newly recognised“sub-bistable” mode of excitation for a marker comprising a LBJmaterial, describe how the dipole length of the LBJ material in thedirection of the drive field is an important parameter for enablingharmonic response and detection. The inventors therefore teach providinga number of wires, for example in a tripod arrangement, such that thedipole length in any given direction is substantially similar. Thisenables a more uniform response to be achieved and provides one with theability to measure the distance from the marker to a detection probe.

However, the provision of a satisfactory marker having the requireduniform response with the same dipole length in each direction, doesencounter a number a problems. In this respect, an implantable markerfor locating a lesion is generally inserted through a small diameterdeployment device requiring the marker to be able to reconfigure from <2mm diameter to its final shape with the same dipole length in eachdirection. The tripod arrangement of the material or other 3D shape withsimilar dipole length in each direction results in a marker that hasthin sections making it fragile or vulnerable to movement. If the markerfails to deploy correctly, then the response will be non-uniform andinaccurate.

Therefore, there is a need for a marker which is more robust andpreferably does not need to make a reconfiguration on deployment.

The present invention aims to address this need.

SUMMARY OF THE INVENTION

According to a first aspect of the present invention there is provided amagnetic marker comprising:

-   -   at least one implantable marker, the implantable marker        comprising at least one piece of magnetic material that exhibits        a large Barkhausen jump (LBJ) in its magnetisation curve,        wherein the LBJ material comprises at least one overlapping        loop, said at least one loop being maintained during detection        of the marker.

In a preferred embodiment, the marker comprises at least one piece ofLBJ material having at least two full convolutions, preferably more, toform a coil or helix.

Surprisingly, the inventors have found that a coil of LBJ wire producesa measurable harmonic response in addition to a straight LBJ wire. Athigher fields and larger diameter coils, this is a switching responsesimilar qualitatively to the classic bistable switching described in theprior art. However, at lower fields and with smaller diameter coils, theresponse is ‘sub-bistable’ as described in the Applicant's co-pendingPatent Application No. GB1801224.5.

Furthermore, while a single straight LBJ wire provides an axial responsethat is much greater than the transverse (perpendicular to the axis)response, more surprisingly the inventors have found that a coil of LBJwire when excited in either the bistable or sub-bistable mode, has alarger transverse response than axial response, even when its length isseveral times its diameter.

The marker according to the invention may comprise a coil or helix ofLBJ material having any number of complete turns or convolutions. Thediameter and/or the pitch of the coils may be varied to adjust theresponse, including the ratio of the transverse to axial response inorder to provide a more uniform response. For example, the marker may beformed of convolutions of an identical pitch or the convolutions mayhave a varying pitch along the longitudinal axis or length of themarker. Similarly, the marker may be formed of convolutions of anidentical diameter or the convolutions may vary in diameter along thelength of the marker, for example to provide a marker that isconical-shaped, barrel-shaped or hour glass shaped.

It is preferable to provide at least one axial member comprising atleast one piece of LBJ material extending at least partially through thecentre of the coiled marker to adjust the ratio of the transverse toaxial response of the marker in order to provide a more uniformresponse. The at least one axial member may be in the form of a separatepiece of material inserted through the coil or may be formedcontinuously with the coil at one or both ends of the marker.

The marker according to the invention may also comprise multiple coils.The multiple coils may be interwoven together or may comprise a coilhaving convolutions of a smaller diameter contained within a coil havingconvolutions of a larger diameter. The pitch may differ in the differentcoils but it is preferably similar to enable close meshing of multiplecoils.

The marker may also be provided with at least one tissue engagementmember to aid securement of the marker to tissue at a lesion site. Forexample, one or both ends of the coiled marker may be provided with ahook or prong, preferably being formed integrally with the marker.

Preferably, the marker comprises less than 5 mg of LBJ material. Thematerial may be provided in the form of a wire that is wound into a coilof the required pitch and diameter. Examples of such materials include,but are not limited to, iron-, cobalt- and nickel-rich glass-coatedamorphous microwires, iron-silicon-boron based amorphous microwires,iron-cobalt based amorphous microwires, and/or bulk metallic glasswires.

Preferably, the marker is deployable from a needle having an innerdiameter of less than 2 mm. More preferably, the aspect ratio of themarker prior to deployment is >3. It is preferable for the coiled markerto be deployable in its final form without the need for a shapetransition, thereby reducing the likelihood of the marker failing todeploy correctly which may affect the accuracy and uniformity of anydetected response from the marker.

The wires may be coated or provided within a housing. Preferably, theLBJ wire is coated or provided within a tube of non-magnetic material toprovide composite properties such as strength, stiffness, flexibilityand biocompatibility. For example, the wire may be coated with a polymercoating such as FEP, Parylene, PTFE, ETFE, PE, PET, PVC, or silicone oran epoxy-based encapsulant. Alternatively, the wire may be encased in atube prior to being formed into the required coiled marker shape.Suitable materials for the tube include Nitinol, titanium, stainlesssteels and other biocompatible alloys. Preferably the material isnon-magnetic and has a relatively low conductivity. More preferably, thehousing is formed from a material having a resistivity greater than2×10⁻⁷ Ωm. The resistivity may also be increased through selectivecutting of the tube such as with an interrupted laser cut spiral. Thismay also aid in winding of the tube.

The tube, especially if selectively cut, may be further coated or housedwithin a biocompatible sheath prior to coiling and/or the coiled markermay be housed or coated in a similar sheath. Preferably this sheath isalso an insulating layer.

The marker housing may be formed from a moulded or extruded material.For example, a polymer may be extruded around the magnetic wire to forma coated wire that can then be formed into a loop. Suitable materialsfor the coating or overmoulding include PEEK, PEKK, polyethylene,polypropylene, polyester, polyurethane, polyimide, polyether blockamide, polyamide, PTFE, FEP and silicones.

In one embodiment, a marker according to the present invention includesa housing comprising one or more strands of material which are woundaround the magnetic material, for example in the form of a helix, toform a more robust construction prior to forming into the final markershape. Preferably the surrounding material completely encloses themagnetic marker material. The strands of the surrounding material couldbe formed from one material or from more than one type of material toobtain a different profile of material properties such as strength,stiffness, resistivity, or echogenicity. The surrounding material couldbe wound in a single layer or in multiple layers within the scope of theinvention. Similarly, the layers could be wound in alternate senses ordirections, and could comprise different materials or cross sections andmay be further coated or housed within a biocompatible sheath prior tocoiling and/or the coiled marker may be housed or coated in a similarsheath.

Thus, the marker is formed of a coil that can be deployed from a needlein its final form without the need for a shape transition. However, inan alternative embodiment, the marker can comprise a resilientlydeformable tube containing the LBJ wire such that the coil expands ondeployment to a larger size.

It is to be appreciated that the cross section of the marker is notlimited to a particular shape. For example, the marker may be round,rectangular or triangular in cross-section. It may be preferable toprovide a marker having a section in which there is a substantiallystraight side, for example rectangular or triangular in order to provideangles at which there is an increased magnetic response relative toother angles, e.g. when a straight section is aligned with theexcitation field.

The marker for use in the present invention is preferably configuredsuch that when implanted into the body the magnitude of a harmonicresponse from the marker when interrogated by an alternating magneticfield is substantially the same when measured from any directionrelative to the marker, and allows the distance between the probe andthe marker to be determined.

According to a second aspect of the present invention, there is provideda detection system for locating a marker, the system comprising:

-   -   a magnetic marker according to the first aspect of the present        invention;    -   at least one drive coil arranged to excite the marker with an        alternating magnetic field and at least one sense coil arranged        to detect a signal received from the excited marker;    -   a magnetic field generator arranged to drive an alternating        magnetic field through the at least one drive coil; and    -   at least one detector arranged to receive the signal from the        sense coil and detect one or more harmonics of the drive        frequency in the received signal.

Depending upon the size and configuration of the marker, the drive coilmay excite the marker above a threshold that initiates bistableswitching behaviour of the LBJ material. Alternatively, and morepreferably, the at least one drive coil excites the marker below theswitching field required to initiate bistable switching behaviour of theLBJ material of the marker.

Preferably, a harmonic response is used to determinelocation/distance/proximity of the marker from a probe. More preferably,the ratio of maximum to minimum harmonic response with direction is <3.

In a preferred embodiment of this aspect of the invention, both thedrive and sense coils are provided in a handheld probe. Alternatively,only the sense coil may be provided in a handheld probe. In thisembodiment, a larger drive coil may be provided external to the probe toenable an increased magnetic field to be generated at the marker site.For example, the drive coil may be provided within a pad for placementnear or beneath a patient.

The detection system preferably comprises an output module forprocessing the received harmonic signal and providing at least oneindicator to the user relating to a location of the marker relative tothe sense coil, for example an indication of the proximity, distance,direction and/or orientation of the marker with respect to the sensecoil.

More preferably, the system processes one or more aspects of theharmonic response of the marker, such as the magnitude of one or moreodd harmonics (e.g. 3^(rd) and 5^(th)), even harmonics (e.g. 2^(nd),4^(th) and 6^(th)) or a combination of both or the ratios of theseharmonics to each other or to the fundamental frequency. Appropriatefilters may be provided to enhance the drive and sensed signals.

The output module may include a visual display or sound generator.

According to a third aspect of the present invention there is provided amethod of detecting an implantable marker, the implantable markercomprising at least one piece of magnetic material that exhibits a largeBarkhausen jump (LBJ) in its magnetisation curve, wherein the LBJmaterial comprises at least one overlapping loop maintained in themarker during detection thereof, the method comprising applying analternating magnetic field to the marker to excite the marker toinitiate bistable or sub-bistable switching behaviour of the LBJmaterial of the marker; and detecting one or more harmonics of the drivefrequency of a signal received from the excited marker caused by achange in magnetization of the marker.

Preferably, the marker is excited below the switching field required toinitiate bistable switching, wherein the application of the alternatingmagnetic field to excite the marker below the switching field results ina sub-bistable response being detected for the marker.

Preferably, the drive frequency is above 1 kHz, preferably being in therange 1-100 kHz, especially 10-40 kHz.

The method preferably includes measuring an aspect of the harmonicresponse of the marker to provide an output relating to the location ofthe marker. For example, this may be the amplitude of one or more oddharmonics, even harmonics or a combination of both, the ratios of theseharmonics to each other or to the fundamental frequency. Appropriatefiltering and processing of the signals may be provided to enhance theoutput provided by the method.

BRIEF DESCRIPTION OF THE DRAWINGS

For a better understanding of the present invention and to show moreclearly how it may be carried into effect, reference will now be made byway of example only, to the accompanying drawings, in which:

FIG. 1A is a schematic diagram of a detection system for use with amarker according to the invention, the detection system forming part ofthe prior art;

FIG. 1B illustrates the components of the detection system shown in FIG.1A in further detail;

FIG. 2 illustrates use of a detection system to locate an implantedmarker;

FIGS. 3A and 3B illustrate a third harmonic (H3) response (arbitraryunits) from an LBJ wire as the magnitude of the 100 Hz excitation fieldis increased, shown with both log-log and log-linear scalesrespectively;

FIG. 3C shows the time-domain response in the sub-bistable region atpoint A in the top graph of FIG. 3A when driven by a sinusoidal wave;

FIG. 3D shows the time-domain response in the bistable region at point Bin the graph of FIG. 3A when driven by a sinusoidal wave;

FIG. 3E is the Frequency domain response from an LBJ wire in thesub-bistable and bistable switching modes at 100 Hz excitationfrequency;

FIG. 4 is a block diagram of a magnetic detection system for use with amarker of the present invention;

FIGS. 5A and 5B illustrate a deployment device for deployment of amarker according to the present invention;

FIGS. 6A to 6D illustrate embodiments of a marker according to thepresent invention;

FIGS. 7A to 7C illustrate further embodiments of a marker according tothe present invention;

FIGS. 8A and 8B illustrate alternative embodiments of a marker accordingto the present invention, the markers each having a variable pitch.

FIGS. 9A to 9C illustrate yet further embodiments of a marker accordingto the present invention, wherein the markers have convolutions ofvarying diameter along the length of the coil;

FIGS. 10A and 10B illustrate yet still further embodiments of a markeraccording to the present invention, wherein the markers include multipleintermeshed coils;

FIGS. 11A and 12A are side views and FIGS. 11B and 12B are end-on viewsof a marker according to alternative embodiments of the presentinvention;

FIG. 13 illustrates yet another embodiment of a marker according to thepresent invention;

FIG. 14 illustrates still yet a further embodiment of a marker accordingto the present invention;

FIGS. 15A and 15B illustrate another embodiment of a marker according tothe invention wherein the magnetic material is part of a stranded wireor braid;

FIGS. 16A and 16B illustrate yet another embodiment of a markeraccording to the invention wherein the magnetic material is within atubular housing;

FIGS. 17A and 17B illustrate yet still a further embodiment of a markeraccording to the invention wherein the magnetic material is providedwith a coating;

FIGS. 18A to 18C illustrate examples of possible cross-sections for amarker according to the present invention;

FIG. 19A illustrates the harmonic response for a marker according to theprior art, with the wire lying along the 0-180° axis in the chart;

FIG. 19B illustrates the harmonic response from the marker shown in FIG.6A, with the wire lying along the 0-180° axis in the chart;

FIG. 19C illustrates the harmonic response from the marker shown in FIG.6B, with the wire lying along the 0-180° axis in the chart;

FIG. 19D illustrates the harmonic response from the marker of FIG. 7B,with the wire lying along the 0-180° axis in the chart; and

FIG. 20 illustrates the marker magnetic H3 response with distance from aprobe for the marker of FIG. 7B, wherein each line is one orientation,and orientations of 0, 30, 45, 60 and 90 degrees to the long axis of themarker are shown.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to a magnetic marker that can be implantedfor marking a site in the body, for example the site of a lesion andsubsequently be detected and localised using a handheld probe. Theinvention also describes a detection system and method for locating theposition of the implanted marker in the body.

FIGS. 1A and 1B of the accompanying drawings show schematic diagrams ofan example of a detection system according to the prior art that may beused to detect a marker according to the present invention. Thedetection system comprises a probe 2 connected to a base unit 4. Theprobe has one or more drive coils 8 (see FIG. 1B) that generate analternating magnetic field to excite a magnetic marker 6. The probe 2 ofthe detection system further contains one or more sense coils 10arranged to detect the changes in the magnetic field caused by thechange in magnetisation of the marker.

FIG. 2 illustrates how the marker 6 may be implanted into a patient'sbreast and then located using the probe 2.

It is desirable to provide improved markers for enhanced localisation bythe probe. The Applicant's co-pending Application No. GB1801224.5describes one such marker. The marker comprises at least one piece ofmagnetic marker material having a large Barkhausen discontinuity in itsmagnetisation curve, also known as a large Barkhausen jump material (ora LBJ material). When the LBJ material is exposed to an externalmagnetic field whose field strength opposing the instantaneous magneticpolarization of said length of material exceeds a predeterminedthreshold value, the switching field H_(SW), its magnetic polarizationundergoes a rapid reversal. This reversal of magnetisation generates amagnetic pulse with rich harmonic components. Conventionally, themarkers are sized to be above the so-called ‘critical length’, that isthe length at which the magnetization can undergo the full bistabletransition or ‘flipping’ behaviour which is required to generate asignificant harmonic response. However, the inventors found that aharmonic response can be obtained from markers significantly below theircritical length and/or below the switching field H_(SW) in a newlyrecognized “sub-bistable” mode and that this is advantageous for use forlocalization of the implantable marker.

FIGS. 3A to 3E illustrate this bistable and so-called “sub-bistable”behaviour of the LBJ material which may be incorporated into animplantable marker. FIGS. 3A and 3B illustrate a third harmonic (H3)response (arbitrary units) from an LBJ wire as the magnitude of the 100Hz excitation field is increased, shown with both log-log and log-linearscales respectively. As demonstrated, when a piece of cobalt-ironamorphous LBJ microwire above the critical length is excited with analternating magnetic field at 100 Hz, the third harmonic (H3) responseis shown in FIG. 3A. H3 is here taken as representative of the harmoniccontent of the marker response. Once an H3 response is distinguishablefrom noise, it increases in an approximately linear relationship withexcitation field. This continues until the switching field is reached,at which point the response increases dramatically in magnitude as thebistable switching is initiated (region B in FIG. 3A). It is this pointat which LBJ above a critical length is normally identifiable. Thelog-linear and log-log scales clearly illustrates the change in mode.However, FIG. 3A shows that by using the “sub-bistable” mode (region Ain FIG. 3A), the marker can be detected even when the field is almost 2orders of magnitude lower than the switching field required for bistablebehaviour. This means that for a given drive field, the marker can bedetected at a much greater distance from the probe.

FIG. 3C shows the time-domain response in the sub-bistable region whendriven by a sinusoidal wave. It is seen as a distorted sine wave, incontrast to the bistable time-domain response which shows the classicshort pulses as the magnetisation reverses (see FIG. 3D). In thefrequency domain, the rich harmonics of the bistable mode contrast withthe less rich harmonic response of the sub-bistable mode (see FIG. 3E).However, such harmonic response is still richer than the response fromnon-bistable amorphous wires and thus this response may be used toaccurately identify a marker even when the length of wire is below the‘critical length’ and the excitation field is below the ‘switchingfield’.

FIG. 4 of the accompanying drawings shows a block diagram of a magneticdetection system which may be used to locate a marker according to theprior art or according to the invention. A frequency generator 12 forexample an oscillator or waveform generator (f_(D) is 100 Hz to 50 kHz)generates a preferably sinusoidal alternating signal which excites oneor more drive coils 8. The one or more drive coils generate analternating magnetic field that extends into the tissue containing amagnetic marker 6 comprising at least one piece of a large Barkhausenjump material (LBJ).

The alternating magnetic field excites the marker 6 and themagnetisation of the marker leads to the generation of harmoniccomponents in the field. Depending on the arrangement of the marker, theharmonics may be odd harmonics, (3^(rd), 5^(th), 7^(th) etc.) or evenharmonics (2^(nd), 4^(th), 6^(th) etc.) or a combination of both odd andeven harmonics. The marker is detected by measuring the magnitude of oneor more of the harmonic frequencies directly or by measuring the ratioof the magnitude of one or more harmonics to others or to the magnitudeof the fundamental frequency.

The response from the marker is detected by one of more sense coils 10to generate a sense voltage or current. The sense coils may be in ahandheld or robotic probe. A high-pass or notch filter 14 may bearranged to filter out or attenuate at least components of the sensesignal at the drive frequency so that the resulting signal has minimalcontent at the drive frequency and comprises higher harmonic componentsof the signal, for example the second, third, fourth, fifth or seventhorder harmonics or combinations of these. The filter may take the formof a passive LCR type filter comprising a known arrangement of forexample capacitors, inductors and resistors or an active filtercomprising a known arrangement for example based on one or more op-amps.

The filtered signal may be fed to a harmonic detection circuit 16 whichamplifies one or more harmonic components of the signal and converts thesignal 18 to a measure of distance from the probe to the marker. A userdisplay and sound generator 20 provides a visual and audio output to theuser indicating for example, the proximity of the marker or themagnitude of the magnetic signal. The system may indicate the proximity,size, distance to, direction or orientation of the marker, orcombinations of these.

When a straight piece of LBJ wire is excited, the magnetic response itgives is directional, that is there is a greater response along the axisof the wire and a much lower response in a direction perpendicular tothe wire. For this reason, the inventors co-pending ApplicationGB1801224.5 describes how the dipole length of the LBJ material in thedirection of the drive field is an important parameter for enablingharmonic response and detection and discloses the use of a number ofwires, for example in a tripod arrangement, such that the dipole lengthin any given direction is substantially similar. However, such markershave thin sections making them fragile or vulnerable to movement. Thiscan make satisfactory deployment of the marker difficult.

FIGS. 5A and 5B show an example of a deployment system according to theprior art that may be used to deliver a marker to a surgical site. FIG.5A shows a deployment device 200 comprising a needle 202 and a plunger204. In use, the needle is inserted into the target tissue under imagingguidance. The deployment device is arranged such that on depression ofthe plunger, the magnetic marker is deployed from the end of the needleinto the target tissue. FIG. 5B shows a detail of the distal end of thedeployment device 200 containing a magnetic marker 6 in the needle 202together with a plunger 204.

It is critical that the marker 6 deploys correctly from the needlebecause otherwise the similarity or identity of the dipole length ineach direction will be affected, leading to a non-uniform and inaccurateresponse.

The present invention provides improved markers that contain LBJmaterial which may be detected using their conventional bistablebehaviour or using the recently identified “sub-bistable” mode. Theinventors have surprisingly found that markers that have a LBJ materialformed into a coil or loop produce a measurable harmonic response. Thiswas not to be expected because classic switching behaviour occursthrough a cascade or domino effect in which the magnetic domains in theLBJ wires all flip at one time, and thus alignment of all the domainswith the driving magnetic field is key. Domains not substantiallyaligned with the field will not flip or switch, thus resulting in theuse of straight wires for detection. Thus, the skilled person wouldconsider the use of any other configuration to be counter-intuitivebased on the prior art literature. The coiled markers according to theinvention demonstrate switching response similar qualitatively to theclassic bistable switching described in the prior art at higher fieldsand larger diameter coils, while at lower fields and with smallerdiameter coils, the response is ‘sub-bistable’ as described inGB1801224.5.

Furthermore, while a single straight LBJ wire provides an axial responsethat is much greater than the transverse (perpendicular to the axis)response, more surprisingly, the inventors have found that a coil of LBJwire when excited in the sub-bistable mode (and indeed the bistablemode), has a larger transverse response than axial response, even whenits length is several times its diameter.

FIGS. 6A to 6D illustrate different embodiments of a marker 6 accordingto the invention. Each marker 6 comprises a coil 6 a of magneticmaterial. FIG. 6A shows a simple coil of magnetic marker material. FIG.6B shows a coil 6 a with a further piece of magnetic material, forexample in the form of a rod of wire 6 b placed axially inside the coil.FIG. 6C shows a coil 6 a with one end of the coil folded back into thecentre of the coil to form an axial element 6 c inside the coil. FIG. 6Dshows a further embodiment in which both ends of the coil 6 a are foldedback through and towards the centre of the coil to form axial elements 6d, 6 e inside the coil. These axial elements inside the coil increasethe magnitude of the axial magnetic response which can be used to obtainthe desired uniformity or asymmetry of response.

FIGS. 7A to 7C shows coiled markers according to the present invention,with a different pitch of the coil 6 a compared to the tight pitch shownin FIGS. 6A to 6D. FIG. 7C shows a coiled marker 6 in which the ends 6f, 6 g continue axially outside the coil. The extended ends increase themagnitude of the axial magnetic response which can be used to obtain thedesired uniformity or asymmetry of response.

FIGS. 8A and 8B show embodiments of a coiled marker according to thepresent invention in which the pitch of the coil varies through itslength. FIG. 8A shows a coil with a central region 6 h with a smallerpitch and outer regions 6 i with a larger pitch. In contrast, FIG. 8Bshows a coiled marker having a central region 6 j with a larger pitchand outer regions 6 k with a smaller pitch. It is to be appreciated thatthe pitch can be varied in any way along the length of the marker indiscrete or continuous ways within the scope of the invention. As can beseen from the values in Table 1 below, an increase in the pitch causesthe magnitude of the axial magnetic response to increase relative to thetransverse response. This can also be used to obtain the desireduniformity or asymmetry of response.

FIGS. 9A to 9C illustrate alternative embodiments of a marker accordingto the invention wherein the diameter of the marker varies along thelength of the marker. For example, FIG. 9A reduces the diameter of theconvolutions of the coil from one end of the coil to another to form aconical shaped marker. FIG. 9B reduces the diameter of the convolutionsof the coil from both ends of the coil towards the centre to form ahourglass shaped marker. FIG. 9C increases the diameter of theconvolutions of the coil from both ends of the coil towards the centreto form a barrel shaped marker. Varying the diameter of the convolutionsof the coiled marker along its length is advantageous to modify themagnetic response from different directions. Coiled makers having bothdifferent diameters and pitches fall within the scope of the invention.Increasing the number of coils and their diameter increases themagnitude of the response in a cumulative fashion, although there aresome losses due to the proximity of the coils to each other. Thus thesearrangements could be used to modify the uniformity of the magneticresponse as desired.

Further embodiments of a marker according to the present invention areshown in FIGS. 10A and 10B, wherein the marker is provided with multiplecoils combined or intermeshed within the marker. FIG. 10 a illustrates amarker with two coils 6 l, 6 m and FIG. 10B shows a marker with threecoils 6 n, 6 o, 6 p. Each of the coils that are combined could have adifferent diameter and/or pitch within the scope of the invention.However, it is preferable for the multiple coils to have similardiameters and pitches such that they can mesh closely together as shownin FIGS. 10A and 10B to maximise the efficient use of space within themarker envelope. Additional coils increase the magnitude of the responsein an approximately additive fashion, although there are some losses dueto the proximity of the coils to each other.

FIGS. 11A to 13 illustrate further embodiments of the marker in whichadditional features are present to aid engagement with tissue once themarker has been implanted into a patient. Examples include a hook orprong or conical coil shapes, and be at one or both ends of the marker,or protrude from the side of the marker. For example, FIGS. 11A and 11Bshow a coiled marker wherein the ends of the coil extend away from thecoil 6 to provide engagement members 6 q. FIGS. 12A to 12B has theseends shaped to form a hook-like engagement feature 6 r. The features maybe formed from the same material as the coil or from a differentmaterial. The features may further be arranged to compress within themarker deployment device and then, resiliently or via a shape memorychange, transform into their final shape upon deployment. Such featuresmay be adapted to aid engagement with a particular kind of tissue. Forexample a larger diameter coil or conical coil shape, such as that shownin FIG. 13 , may be beneficial for locating in a lumen, blood vessel, orairway in the lung. Barb shaped features may be beneficial for locatingin breast tissue or a biopsy cavity.

FIG. 14 shows yet another embodiment of a marker according to theinvention in which a smaller coil 6 s is combined with a larger outerdiameter coil 6 t within the marker. This is advantageous in order toprovide more magnetic material within the same space envelope defined bya narrow gauge delivery needle. Again, the coils could be differentdiameters and pitches within the scope of the invention but preferablyare closely wound with minimal space between each turn in the coil inorder to maximise the efficient use of space within the marker envelope.

The LBJ magnetic material that is wound into coil as herein describedmay be combined with other materials to improve the marker. For example,the marker may be packaged within other materials. In this respect,markers for implantation need to be both biocompatible to prevent areaction with body tissue, and robust. Some preferred magnetic materialsare thin (wires below 0.15 mm in diameter), and containnon-biocompatible materials. Therefore, to improve the biocompatibilityand robustness of the marker, it is preferable to provide a housing orcoating for the magnetic material. FIGS. 15A to 18B of the accompanyingdrawings illustrate alternative combinations of the magnetic materialwith other materials to form the packaged marker. This may be in theform of a coating 22, as shown in FIGS. 17A to 17B. For example, themagnetic wire may be coated with a polymer coating such as FEP,Parylene, PTFE, ETFE, PE, PET, PVC or silicone, or an epoxy-basedencapsulant. Alternatively or additionally, the magnetic material may beencased in a tube 24 prior to being formed into the required markershape, as shown in FIGS. 16A and 16B (shown in the pre-formedcondition). This arrangement improves the robustness of the magneticmaterial. Suitable materials for the tube include Nitinol, titanium,stainless steels and other biocompatible alloys. Preferably the materialis non-magnetic and has a relatively low conductivity, in order not toinfluence the magnetic response of the marker. Preferably the volumeresistivity is greater than 2×10⁻⁷ Ωm (Ohm-metres) in order to minimisethe production of Eddy currents within the housing which could affectthe magnetic response.

In a preferred embodiment a biocompatible and insulating coating orsheath such as FEP, Parylene, PTFE, ETFE, PE, PET, PVC or siliconefurther surrounds the tube 24. This insulating layer stops conductionbetween the turns within the coils further reducing the effects of Eddycurrent on the magnetic response of the marker.

Table 2 below shows the influence of the conductivity of the tubematerial on the harmonic response for straight lengths of an LJB wire indifferent tube materials. The signal from the LBJ wire in the coppertube with a material resistivity of 0.17×10⁻⁷ Ωm is at least 16 timeslower than the signal from similar wires in tubes made with othermaterials with a higher resistivity of greater than 2×10⁻⁷ Ωm. The useof selective cutting of the tube such as with an interrupted laser cutspiral, which also supplies flexibility for coiling, may also be used toincrease resistance and reduce the production of Eddy currents. Thepolymer coating may be applied before or after the material or tube isformed into a coil.

In a preferred embodiment, the marker housing could be formed from amoulded or extruded material. For example, a polymer may be extrudedaround the magnetic wire to form a coated wire that can then be formedinto a loop or coil. Any of the embodiments above could also beovermoulded with a polymer to form a marker. The advantage of such anembodiment is that the polymer could provide biocompatibility and alsomake the manufacturing process simpler and less costly. The use ofpolymers also minimises any Eddy current effects seen with metalcoatings or housings that could affect the magnetic response. Suitablematerials for the coating or overmoulding include PEEK, PEKK,polyethylene, polypropylene, polyester, polyurethane, polyimide,polyether block amide, polyamide, PTFE, FEP, PET and silicones.

In another preferred embodiment, a marker according to the presentinvention includes a housing comprising one or more strands of material26 which are wound around the magnetic material to form a more robustconstruction prior to forming into the final marker shape. FIGS. 15A and15B show, for example, a piece of marker material 6 with 6 strands of adifferent material 26 a-f wound around it in a helical arrangement (seeFIG. 15B). The surrounding material could be in the form of wires withround, rectangular or other cross section. Preferably the surroundingmaterial completely encloses the magnetic marker material. The strandsof the surrounding material could be formed from one material or frommore than one type of material to obtain a different profile of materialproperties such as strength, stiffness, resistivity, magnetic response,radiopacity or echogenicity. The surrounding material could be wound ina single layer or in multiple layers within the scope of the invention.Similarly, the layers could be wound in alternate senses or directions,and could comprise different materials or cross sections. Suitablematerials for the surrounding material include those listed above forthe tube embodiment of FIGS. 16A and 16B. Various braids or weavesincluding the magnetic material in wire form could also be envisagedwithin the scope of the invention.

In any of the above embodiments, the marker may comprise a resilientlydeformable member (tube, wire strands or coating) containing the LBJwire such that the coil expands on deployment to a larger size. Theexpansion may be driven elastically by a resiliently deformable materialor by a shape memory transition material such as nitinol.

In a further embodiment, the cross section of the marker may take anumber of forms including round, rectangular or triangular, as shown inFIGS. 18A to 18C respectively. In certain instances, a marker having asection in which there is a substantially straight side (such as inFIGS. 18B and 18C) may be advantageous in order to provide angles atwhich there is an increased magnetic response relative to other angles,e.g. when a straight section is aligned with the excitation field.

Table 1 below illustrates characteristics of markers according to theinvention and their H3 magnetic response. Embodiments shown in FIGS. 6to 10 of the drawings are identified in column 1.

TABLE 1 Aspect ratio Ratio max:min Diameter Length Number Pitch (length:H3 magnetic Dominant Housing Marker (mm) (mm) of Turms (mm) diameter)response Direction Material Prior Art straight 0.1  4 none N/A 40.0 39.1  Axial None length of wire Single Coil 1.26 7 22 0.32 5.6 19.8 Perp. Cu Single Coil 1.26 7 11 0.64 5.6 6.6 Perp. Cu Single Coil 1.26 78 0.88 5.6 5.5 Perp. Cu Single Coil 1.26 7 4.5 1.56 5.6 1.4 None CuSingle Coil 1.06 8 1.5 5.3 7.5 4.7 Axial Cu Single Coil 1.16 6 2 3.0 5.21.6 None Cu Single Coil 1.03 6 17 0.35 5.8 10.9  Perp. Cu (FIG. 6A) Coil& Axial wire (FIG. 6B) Coil: 1.03 6 17 0.35 5.8 1.2 None Cu Axial wire:0.1    3.2 none N/A None Single Coil 1.01 7 8.5 0.82 5.6 1.2 None Ti(FIG. 7B) Variable Pitch 1.01 8 1 2.5 7.9 2.2 Perp. Cu Coil (FIG. 8A) 90.33 1 2.5 Mullti-coil, 3 coils 1.06 7 3 × 3 2.33 6.6 1.6 None Cu (FIG.10B)

Table 2 below illustrates the effect of the housing material of themarker on the magnitude of H3 response at a distance of 20 mm for aprobe of a straight length of Co—Fe LBJ material of 4 mm.

TABLE 2 Hosing Housing H3 response Housing Diameter Length HousingMaterial relative Ratio max:min H3 Material (mm) (mm) Resistivity (Ωm)to copper magnetic response Copper 0.29 4 1.7 × 10⁻⁸  1  3 316 StainlessSteel 0.50 4 7.4 × 10⁻⁷ 16 23 Titanium 0.51 4 5.2 × 10⁻⁷ 17 26 Nitinol0.33 4 7.6 × 10⁻⁷ 19 41

Table 3 below shows how the magnitude of H3 response varies withdiameter at a distance of 20 mm for a marker with similar coil pitchesfor coils in both 304ss and PET as well as demonstrating the increasedresponse from coils in a material where there is less opposing eddycurrents e.g. coils (PET), showing the increase in relative response perturn for the single coils with diameter. It also demonstrates theincreased signal from a coil of smaller diameter inside a coil of largerdiameter (FIG. 14 ). All coils are measured in a perpendicularorientation.

TABLE 3 Magnetic Signal per H3 response Material Coil Turn/304ssrelative Coil Diameter Length No of Pitch Ø0.88 mm ø0.88 mm CoilMaterial (mm) (mm) Turns (mm) Signal per turn 304ss coil Single Coil304ss 0.88 5 13 0.39 1 1 A Single Coil 304ss 0.99 7 17 0.41 1.8 2.3 ESingle Coil 304ss 1.10 5 14 0.36 2.9 3.1 B Single Coil 304ss 1.25 5 140.36 3.3 3.5 C Single Coil 304ss 2.02 5 11.5 0.43 6.2 5.5 D Coil Cinside 304ss 1.25 inside 5 14 inside 0.36 inside N/A 6.7 Coil D (9) 2.0211.5 0.43 Single Coil PET 1.1 8 15 0.53 3.9 4.5 F Single Coil PET 1.2 610 0.60 4.6 3.5 G Single Coil PET 1.46 5.8 10 0.58 5.9 4.5 H Single Coil1 PET 2.22 5.4 10 0.54 7.7 5.9 Single Coil J PET 3.26 5.8 10 0.58 10.17.8

FIGS. 19A to 19D show how the response of various markers varies withthe orientation of the marker axis relative to the detection probe, whenthe marker is excited with the probe arrangement of FIG. 1 . In eachcase the long axis of the marker is aligned with the 0-180° axis in thefigure.

FIG. 19A shows the magnetic response from a prior art single cobalt-ironamorphous LBJ microwire. The harmonic (e.g. H3) response is stronger bya factor of almost 40 times in the axial direction versus the transversedirection of sensing. This asymmetry of response would be expected froma straight length of LBJ wire based on the prior art literature, forexample von Gutfeld (von Gutfeld, R J et al., Amorphous magnetic wiresfor medical locator applications, Appl. Phys. Lett., Vol. 81, No. 10, 2Sep. 2002) which describes an axial response many times stronger thanthe transverse response.

FIG. 19B shows the magnetic response from the marker of FIG. 6Aconstructed with a cobalt-iron amorphous LBJ microwire wherein the LBJwire is in the form of a coil. According to the conventional theory, LBJwires need to be straight to produce a harmonic response. However,surprisingly, for a piece of LBJ wire, the coil produces a strongharmonic response. More surprisingly, the transverse harmonic responseis stronger than the axial harmonic response which is contrary to whatwould be expected from the physical aspect ratio (length:diameter) whichin this case is approximately 6 (see Table 1).

The inventors have found that such markers can be combined to create amarker with a more optimal or preferred harmonic response profile.Specifically, it is preferable if the harmonic response at a givendistance from the marker is substantially uniform.

Thus for example, the prior art single straight wire can be combinedwith the coil of FIG. 6A, to obtain the marker of FIG. 6B.

FIG. 19C shows the variation in the harmonic (H3) response from such amarker of FIG. 6B, constructed with a cobalt-iron amorphous LBJmicrowire, as its orientation with respect to the probe is varied. Themarker comprises a coil of fine copper tube containing cobalt-ironamorphous LBJ microwire as the magnetic material, the tube being woundinto a coil with a further length of the same LBJ wire positionedaxially inside the coil. The coil is 1.03 mm in diameter, 6 mm long andhas 17 turns, giving a pitch of 0.35 mm. The axial wire is 3.2 mm long.

It is demonstrated in FIG. 19C that the harmonic magnetic response issubstantially uniform regardless of the direction of detection, andspecifically, the H3 response in the axial direction is similar to thatin the transverse direction. Thus by appropriate choice of coilparameters and choice of additional axial components, the uniformity ofthe harmonic response can be adjusted and optimised to obtain theprofile of response versus direction that is desired. This could beincreased transverse response or axial response, but is most preferablya uniform or equal response regardless of the direction of excitation orsensing. The advantage of a uniform response is that the signal can bereliably and consistently converted into a distance measurement from theprobe to the marker. If the uniformity is poor, the user will obtain adifferent distance measurement depending on the orientation of themarker with respect to the probe which would be confusing. Theuniformity of response can be estimated by measuring the variation ofresponse with orientation of the marker relative to the probe, andcalculating the ratio of the maximum to minimum response.

In the context of this disclosure, a uniform response means that theratio of the maximum to minimum magnitude of the response being measured(be it H3, or other magnetic response) is less than 3 and preferablyless than 2. Because the magnetic response when being detected with anarrangement similar to that in FIG. 1 drops off with between the thirdand fifth power of distance, if the ratio of maximum to minimum magneticresponse is less than 2, then the variation in measured distance as theorientation of the marker changes will be within a small range,typically less than ±1-2 mm.

FIG. 20 shows plots of H3 magnetic response versus distance (using theconfiguration of FIG. 1 ) for the marker of FIG. 7B for a number oforientations of the marker. This illustrates how the accuracy of thedistance determination can be maintained within ±1-2 mm regardless oforientation of the marker relative to the probe. Table 1 above shows themax:min ratio of H3 response for a range of markers of differentconstructions.

The uniformity of response can also be varied by adjusting the pitch,number of turns/convolutions, length, diameter, shape, cross section andend configuration of the coil, and by varying the diameter or pitch ofthe turns at different points along the length of the coil.

FIG. 19D shows the response from the embodiment of FIG. 7B which has anincreased pitch. The marker comprises a coil of cobalt-iron amorphousLBJ microwire with length 7 mm, diameter 1.01 mm, and 8.5 turns giving apitch of 0.82 mm.

By increasing the pitch compared with the marker of FIG. 6A, the axialharmonic (H3) response can be increased with respect to the transverseharmonic to make the response substantially uniform, regardless of thedirection of sensing. In this case the max:min ratio of the H3 responseis 1.2.

If the pitch is increased to improve the uniformity of the response, thelength of the marker for a given magnitude of response will increase, orthe number of convolutions in a given length of marker will be reduced.The inventors have found that in this case, more than one coil can becombined in the form of a multi-start helix to increase the responsewhile maintaining the small size of the marker. FIGS. 10A and 10B showtwo such examples, one with 2 and one with 3 coils respectively,combined within the marker. In these examples the pitches of thecombined coils are the same, but it is to be appreciated that the pitchof the combined coils could be varied to obtain the desired profile ofresponse.

The present invention provides a new and improved magnetic marker thatmay be used in a system and method for detecting the marker, therebyenabling a lesion for surgical excision to be located. The markercontains at least a piece of LBJ magnetic material that is wound into acoil having at least one, preferably more, convolutions. The marker maybe excited at the switching field (bistable mode) or at a field lowerthan the bistable switching field (sub-bistable mode) and the generatedharmonics measured from any direction to determine the position andorientation of the marker. In embodiments, the marker may also beprovided below the critical length of the LBJ material required toenable bistable switching behaviour.

The invention claimed is:
 1. A magnetic marker comprising: animplantable marker comprising a magnetic material that exhibits a largeBarkhausen jump (LBJ) in its magnetization curve, wherein the magneticmaterial defines a loop, the loop being retained in the implantablemarker during detection of the marker following implantation.
 2. Themagnetic marker of claim 1, wherein the loop comprises one or moresections, wherein the one or more sections define a substantiallystraight side.
 3. The magnetic marker of claim 2, wherein the loopdefines one or more angles.
 4. The magnetic marker of claim 3, whereinthe loop is continuous.
 5. The magnetic marker of claim 4, wherein theloop defines one or more angles.
 6. The magnetic marker of claim 5,wherein the loop defines three or more angles.
 7. The magnetic marker ofclaim 5, wherein the loop defines four or more angles.
 8. The magneticmarker of claim 5, wherein the magnetic material is deployable in finalimplantable form without needing a shape transition.
 9. The magneticmarker of claim 5, wherein a length of the loop is several times itsdiameter.
 10. The magnetic marker of claim 4, wherein the loop is formedintegrally.
 11. The magnetic marker of claim 3, wherein the one or moresections are four sections, wherein each section defines a substantiallystraight side.
 12. The magnetic marker of claim 3, wherein the magneticmaterial is coated with a coating or provided within a housing, thecoating or housing having a relatively low conductivity.
 13. Themagnetic marker of claim 12 wherein the coating or housing is formedfrom a material having a resistivity greater than 2×10⁻⁷ Ωm.
 14. Amagnetic marker comprising: an implantable marker comprising a magneticmaterial, wherein the magnetic material exhibits a large Barkhausen jump(LBJ) in its magnetization curve, wherein the magnetic material definesa loop, wherein implantable marker is detectable and localizable using anon-invasive handheld probe, wherein the loop comprises one or moresections, wherein the one or more sections define a substantiallystraight side, wherein the loop defines one or more angles, the loopbeing retained in the implantable marker during detection of the markerfollowing implantation.
 15. The magnetic marker of claim 14, wherein themagnetic material is deployable in final implantable form withoutneeding a shape transition.
 16. The magnetic marker of claim 14, whereinthe loop is continuous.
 17. The magnetic marker of claim 14, wherein theone or more sections are at least two sections, wherein each sectiondefines a substantially straight side.